Koepp M J, Richardson M P, Brooks D J, Cunningham V J, Duncan J S
MRC Cyclotron Unit, Hammersmith Hospital, London, UK.
Epilepsia. 1997 Oct;38(10):1089-97. doi: 10.1111/j.1528-1157.1997.tb01198.x.
Previous [11C]flumazenil (FMZ) positron emission tomography (PET) investigations in patients with idiopathic generalized epilepsy (IGE) have demonstrated nonsignificant global cortical decreases in central benzodiazepine gamma-aminobutyric acid A (GABA[A]) receptor (cBZR) binding or focal decreases in the thalamus and increases in the cerebellar nuclei with no changes in cerebral cortex. We previously reported lower [11C]FMZ binding in cerebral cortex of IGE patients treated with valproate (VPA) than in cerebral cortex of controls. We now report high-resolution three-dimensional [11C]FMZ PET studies in a larger number of subjects using an improved method to detect differences in cBZR between IGE patients and controls and a more powerful longitudinal design to determine the functional effect of VPA.
We compared parametric images of [11C]FMZ volume of distribution (FMZVD) in 10 IGE patients before and after addition of VPA and in 20 normal subjects.
Mean FMZVD was significantly higher in the cerebral cortex (11%, p = 0.009), thalamus (14%, p = 0.018), and cerebellum (15%, p = 0.027) of the 10 IGE patients as compared with that of 20 normal controls. Using statistical parametric mapping, no significant areas of focal abnormality of FMZVD were detected. Addition of VPA was not associated with a significant change in mean FMZVD in any brain area.
Our finding of increased FMZVD in IGE could reflect microdysgenesis or a state of cortical hyperexcitability. Our data suggest that short-term VPA therapy does not affect the number of available cBZR in patients with IGE.
既往针对特发性全身性癫痫（IGE）患者的[11C]氟马西尼（FMZ）正电子发射断层扫描（PET）研究表明，中枢苯二氮䓬γ-氨基丁酸A（GABA[A]）受体（cBZR）结合的全脑皮质整体下降不显著，或丘脑出现局灶性下降，小脑核增加，而大脑皮质无变化。我们之前报道，接受丙戊酸（VPA）治疗的IGE患者大脑皮质中的[11C]FMZ结合低于对照组大脑皮质。我们现在报告一项针对更多受试者的高分辨率三维[11C]FMZ PET研究，该研究采用了改进方法来检测IGE患者与对照组之间cBZR的差异，并采用了更强大的纵向设计来确定VPA的功能作用。
我们比较了10例IGE患者在加用VPA前后以及20名正常受试者的[11C]FMZ分布容积（FMZVD）参数图像。
与20名正常对照相比，10例IGE患者大脑皮质（11%，p = 0.009）、丘脑（14%，p = 0.018）和小脑（15%，p = 0.027）的平均FMZVD显著更高。使用统计参数映射，未检测到FMZVD局灶性异常的显著区域。加用VPA与任何脑区的平均FMZVD显著变化无关。
我们在IGE中发现FMZVD增加可能反映了微发育异常或皮质兴奋性过高状态。我们的数据表明，短期VPA治疗不影响IGE患者中可用cBZR的数量。
